Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in Acute Non-disabling Cerebrovascular Events

NCT ID: NCT01924325

Last Updated: 2013-08-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 10000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-07-31

Brief Summary

Nondisabling cerebrovascular events represent the largest group of cerebrovascular disease with a high risk of recurrent stroke. A recent trial indicated that clopidogrel and aspirin treatment reduced the risk of recurrent stroke and was not associated with increased hemorrhage events, compared with aspirin monotherapy. Apixaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants with less risk of bleeding events.

To estimate whether apixaban is beneficial for acute TIA or minor stroke, a randomized, double-blind, multicenter, controlled clinical trial has been designed. The investigators will assess the hypothesis that a 21-days apixaban regimen is superior to clopidogrel and aspirin dual-therapy for the treatment of high-risk patients with acute nondisabling cerebrovascular event.

Detailed Description

The ADANCE study is a randomized, double-blind clinical trial with a target enrollment of 3,000 Chinese patients. Two subtypes of patients will be enrolled: I, acute disabling ischemic stroke (<24 hours of symptoms onset); II, acute TIA (<24 hours of symptoms onset).

Patients will be randomized into 3 groups:

Ⅰ Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily.

Ⅱ Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21.

Ⅲ Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21.

From day 22 to 3 months, all patients will receive 75-mg dose of clopidogrel long-term antiplatelet therapy.

The primary efficacy end point is percentage of patients with new stroke (ischemic or hemorrhage) at 90 days.

Conditions

Ischemic Stroke; TIA

Keywords

apixaban; clopidogrel; aspirin; new oral anticoagulant; TIA; acute minor ischemic stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dual-antiplatelet Therapy

Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor

Aspirin

Intervention Type: DRUG

a non-steroidal anti-inflammatory drug

placebo

Intervention Type: DRUG

Apixaban 2.5mg

Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

orally active direct factor Xa inhibitor

placebo

Intervention Type: DRUG

Apixaban 5mg

Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

orally active direct factor Xa inhibitor

placebo

Intervention Type: DRUG

Interventions

Apixaban

orally active direct factor Xa inhibitor

Intervention Type: DRUG

Clopidogrel

an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor

Intervention Type: DRUG

Aspirin

a non-steroidal anti-inflammatory drug

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Eliquis; BMS-562247; BMS-562247-01; Plavix; Clopivid; Acetylsalicylic acid

Eligibility Criteria

Inclusion Criteria

• Adult subjects (male or female ≥18 years old)
• Acute nondisabling ischemic stroke (NIHSS ≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
• TIA (neurologic deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with investigational medication within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
• Informed consent signed

Exclusion Criteria

• Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major nonischemic brain disease, on baseline head CT or MRI scan
• mRS score >2 at randomization (premorbid historical assessment) NIHSS ≥4 at randomization
• Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state)
• Contraindication to investigational medications
• Thrombolysis for ischemic stroke within preceding 7 days
• History of intracranial hemorrhage
• Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anticoagulation
• Gastrointestinal bleed or major surgery within 3 months
• Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
• TIA or minor stroke induced by angiography or surgery
• Severe noncardiovascular comorbidity with life expectancy <3 months
• Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test result
• Severe renal failure, defined as Glomerular Filtration Rate (GFR) <30 ml/min Severe hepatic insufficiency (Child-Pugh score B to C)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xijing Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gang Zhao, M.D.

Role: PRINCIPAL_INVESTIGATOR

Neurology Department,Xijing Hospital

Locations

Xijing Hospital

Xi'an, Shaanxi, China

Countries

China

Central Contacts

Xuedong Liu, M.D.

Role: CONTACT

Phone: +86 029 84775055

Email: liuxued@fmmu.edu.cn

Facility Contacts

Fang Yang, M.D. Ph.D.

Role: primary

Other Identifiers

Xijing-ADANCE

Identifier Type: -

Identifier Source: org_study_id